The Metformin-FMD Trial

NCT ID: NCT01610401

Last Updated: 2013-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2013-01-31

Brief Summary

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In acute myocardial infarction early restoration of coronary blood flow is the most effective strategy to limit infarct-size. Paradoxically, reperfusion itself also aggravates myocardial injury and contributes to final infarct size, a process termed 'reperfusion injury'. Ischemia and reperfusion (IR)-induced endothelial dysfunction seems to play a pivotal role in this process, resulting in vasoconstriction and reduced blood flow to the already ischemic tissue. Recently, it has been shown that the glucose-lowering drug metformin is able to limit IR-injury in murine models of myocardial infarction, probably by increased formation of the endogenous nucleoside adenosine. In the current research proposal, the investigators aim to translate this finding to the human in vivo situation, using flow-mediated dilation (FMD) of the brachial artery as a well-validated model of (endothelial) IR-injury.

Detailed Description

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Conditions

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Ischemia Reperfusion Injury Endothelial Function

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pretreatment with metformin

Pretreatment with metformin 500 mg three times a day for 3 days.

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

metformin 500 mg three times a day, for 3 days

No pretreatment.

no intervention

Group Type NO_INTERVENTION

No interventions assigned to this group

Pretreatment with Metformin/caffeine

to study whether caffeine (4 mg/kg intravenously over 10 minutes) attenuates the protective effect of metformin (500 mg three times a day for 3 days) on FMD after ischemia/reperfusion

Group Type ACTIVE_COMPARATOR

Pretreatment with metformin in combination of infusion of caffeine.

Intervention Type DRUG

Pretreatment with metformin 500 mg three times a day for 3 days, in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes) prior to FMD measurement

No metformin, only pretreatment with caffeine

No pretreatment with metformin, FMD measurement after forearm ischemia/reperfusion and infusion of caffeine (4 mg/kg intravenously over 10 minutes).

Group Type OTHER

No pretreatment with metformin in combination with infusion of caffeine

Intervention Type DRUG

No pretreatment with metformin in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes).

Interventions

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Metformin

metformin 500 mg three times a day, for 3 days

Intervention Type DRUG

Pretreatment with metformin in combination of infusion of caffeine.

Pretreatment with metformin 500 mg three times a day for 3 days, in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes) prior to FMD measurement

Intervention Type DRUG

No pretreatment with metformin in combination with infusion of caffeine

No pretreatment with metformin in combination with pretreatment with caffeine (4 mg/kg intravenously over 10 minutes).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age 30-50 years
* Written informed consent

Exclusion Criteria

* Smoking
* Hypertension (in supine position: systolic BP \> 140 mmHg, diastolic BP \> 90 mmHg)
* Hyperlipidaemia (fasting total cholesterol \> 5.5 mmol/L or random \> 6.5 mmol/L)
* Diabetes Mellitus (fasting glucose \> 7.0 mmol/L or random glucose \> 11.0 mmol/L)
* History of any cardiovascular disease
* Concomitant use of medication
* Renal dysfunction (MDRD \< 60 ml/min)
* Professional athletes
Minimum Eligible Age

30 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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N. Riksen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

G.A. Rongen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

D.H. Thijssen, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status

Countries

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Netherlands

References

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El Messaoudi S, Schreuder TH, Kengen RD, Rongen GA, van den Broek PH, Thijssen DH, Riksen NP. Impact of metformin on endothelial ischemia-reperfusion injury in humans in vivo: a prospective randomized open, blinded-endpoint study. PLoS One. 2014 Apr 22;9(4):e96062. doi: 10.1371/journal.pone.0096062. eCollection 2014.

Reference Type DERIVED
PMID: 24755906 (View on PubMed)

Other Identifiers

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Metformin-FMD 001

Identifier Type: -

Identifier Source: org_study_id

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